The Seagulls ensured they will play European football next season for the first time in their history after beating Southampton 3-1.
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Roberto De Zerbi's men are not yet mathematically assured that it will be the Europa League and still need one point from their final two games.
But seventh-placed Aston Villa's inferior goal difference means even successive defeats will most likely be enough to qualify for UEFA's second tier.
City, meanwhile, fresh from lifting the title on Sunday, will aim to continue their 24-game unbeaten run across all competitions.
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Pep Guardiola's men remain in pursuit of a historic treble this term and will be determined to continue their recent momentum.
Brighton v Manchester City: talkSPORT coverage
This Premier League clash will be played on Wednesday, May 24.
Kick-off at the Amex is scheduled for 8pm.
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talkSPORT will have EXCLUSIVE live coverage of the game presented by Adrian Durham.
Commentary will then come from Sam Matterface and former Manchester City manager Stuart Pearce.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream.
You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
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Brighton v Manchester City: Team news
The hosts have a lengthy injury list with Solly March, Adam Lallana, Tariq Lamptey, Jakub Moder and Jeremy Sarmiento all out.
Adam Webster is also a doubt while goalkeeper Robert Sanchez continues to be unavailable having refused to sit on the bench.
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As for City, Guardiola made nine changes for the 1-0 win over Chelsea but he is expected to recall his big stars now that they've had a rest and to avoid them losing match sharpness.
Nathan Ake is the club's only injury concern but Erling Haaland, Kevin De Bruyne and Jack Grealish are all set to be back in from the start.
Brighton v Man City: What has been said?
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Guardiola: "A fifth Premier League in six years, seven in 12, I could not imagine winning five in six.
"I have the feeling we've done something exceptional. It's something extraordinary. People know how exceptional it is.
"But to be considered one of the greatest we have to win the Champions League, otherwise it's not complete.
"You have to win in Europe, the Champions League, to be considered one of the best teams like Manchester United or Liverpool but also it's unfair to say if you don't win it, the Premier League doesn't make sense."
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Brighton v Man City: Match facts
Only Liverpool's Mohamed Salah (7) has been involved in more away Premier League goals against Brighton than Manchester City's Riyad Mahrez, with his five goal involvements against the Seagulls coming in his last four visits to the Amex (2 goals, 3 assists).
Pascal Groß has scored 26 Premier League goals, the joint-most by a Brighton player in the competition, alongside Glenn Murray and Neal Maupay. In the Seagulls' history, only Michael Robinson (37) has more goals in the top-flight overall than Groß.
Manchester City's Phil Foden has scored in all four of his Premier League starts against Brighton, being involved in six goals in total in these four matches (5 goals, 1 assist).
Since Roberto De Zerbi's first game in charge of Brighton in October, their Premier League games have seen more goals than any other club's (104 - 59 for, 45 against). Indeed, only Man City (70) and Arsenal (66) have scored more top-flight goals than De Zerbi's side in this time (59).
There have been 15 instances of a team winning 12 consecutive games in English top-flight history, with Pep Guardiola's Manchester City side accounting for five of those runs (including their current run of 12). They last enjoyed a longer winning run in the Premier League between December 2020 - March 2021 (15).
Brighton have won just one of their seven Premier League games against sides starting the day top (L6), however that victory did come against Manchester City, at the Amex, on MD37 back in 2020-21, coming from two goals down to win 3-2.
Manchester City have won each of their last 25 Premier League games on a Wednesday by an aggregate scoreline of 68-11. It's the longest winning run any side has had on a specific day in the competition's history.
Brighton have won their final home league game in each of the last two campaigns, including a 3-2 win over Manchester City in 2020-21. They last did so in three consecutive seasons between 1990-91 and 1992-93.
Manchester City have never failed to score in a Premier League game against Brighton, netting 33 goals in their 11 meetings for an average of three per game.
Brighton have lost 10 of their 11 Premier League games against Manchester City, with the exception being a 3-2 home win in May 2021.